脑出血大鼠脑组织ICAM-1的表达与脑含水量的变化及药物对其影响

目的探讨脑出血后血肿周围脑组织炎性损伤的病理发展过程。方法健康Wister大鼠72只随机分成脑出血模型组、假手术组、麝香组,分别于3h、24h、72h、7d取血肿周围脑组织检测细胞间黏附因子-1(ICAM-1)的表达及出血侧脑组织含水量的测定。结果与假手术组比较,脑出血组ICAM-1从3h起即有表达,72h达高峰,持续7d仍有表达(P<0.05)。脑含水量在24h后明显增加(P<0.01),7d时与假手术组无显著性差异。结论ICAM-1在血肿周围的高表达推测是脑出血后水肿形成和缺血性损伤的主要原因之一。减少ICAM-1的表达和脑含水量推测是复方麝香注射液的药理机制。     

高血压脑出血患者急性期血肿周围组织的炎症反应特征

目的探讨高血压脑出血患者血肿周围组织的炎症反应特征。方法29例基底节区脑出血患者行微创血肿清除术,按出血后手术时间分为6—24h组、24～48h组及〉48h组,将手术中引流的血肿周围脑组织行白细胞共同抗原（LCA）和细胞间黏附分子-1（ICAM-1）免疫组化染色,并与对照组（非脑病尸检患者6例）进行比较。结果脑出血组脑组织标本免疫组化染色可见LCA、ICAM-1免疫阳性微血管及细胞,与对照组相比,表达量显著提高（均P〈0．01）;各时段组间LCA的表达差异无统计学意义;ICAM-1的表达24～48h组及〉48h组显著高于6—24h组（均P〈0．01）,24～48h组与〉48h组间差异无统计学意义。结论脑出血急性期血肿周围脑组织存在急性炎症反应;ICAM-1的表达在出血后48h内逐渐增多。     

实验性大鼠脑出血COX-2与MAP-2表达及作用

目的探讨实验性大鼠脑出血后脑组织COX-2和MAP-2的表达和两者之间的关系,及对脑组织神经元损伤的作用。方法用体重200³00 g健康的大鼠制作脑出血动物模型,将大鼠随机分为出血组和对照组;出血组分为自体血组和盐水对照组,自体血组按不同时间分为3 h、6 h、12 h、24 h、48 h、72 h、5 d、7 d、14 d、28 d、10个亚组,每组7只,盐水组为6 h组7只;正常对照组7只。用HE动态观察组织病理学改变,用免疫组织化学染色显示出血灶周围COX-2和MAP-2在脑组织内的表达。结果大鼠脑出血后脑组织COX-2于出血灶周围阳性细胞数于3 h增多,出血3 d达高峰,阳性细胞见于病变侧额顶部大脑皮质。脑出血组各时间点COX-2表达高于对照组,差异具有统计学意义(P<0.05);MAP-2表达于出血3 h开始减少,3 d下降到最低。脑出血3 h以后,紧邻血肿周围区MAP-2阳性细胞大量消失。3 d后虽有所增加但与对照组的差异仍有统计学意义(P<0.05)。结论COX-2主要在血肿周围的神经元表达,其高表达可能与血肿后继发性神经元损伤有关,脑出血后COX-2高表达促进了神经元的损伤,使MAP-2表达明显减少。     

黄芪注射液对脑出血大鼠细胞凋亡影响的研究

目的 研究脑出血大鼠细胞凋亡的规律及黄芪注射液对出血后脑组织含水量和血肿周围区细胞凋亡的影响.方法 采用肝素化Ⅶ型胶原酶脑内注入法制作大鼠(160只)脑出血模型.制模后根据药物干预的时间随机分成4个治疗组(手术同时组,术后6 h组、12 h组、24 h组,每组32只)和出血对照组(共32只).各治疗组每日经腹腔给予黄芪注射液1次,各组分别于第4 d及第7 d处死.再从上述5组中各选取12只大鼠用于脑组织含水量测定(干湿法),观察不同时间开始治疗对大鼠脑组织含水量、血肿周围区细胞凋亡(脑组织切片TUNEL荧光染色)的影响.结果 治疗组[出血同时组(第4 d)、6 h组(第4 d、7 d)、12 h组(第4 d)]脑组织含水量较出血对照组明显减少(均P<0.01);脑出血后6 h血肿周围凋亡细胞开始出现,3 d达高峰,7 d后明显减少;各治疗组血肿周围细胞凋亡均明显降低,出血同时治疗组和6 h治疗组比24 h治疗组细胞凋亡率明显降低(均P<0.01);脑出血后存在血管内皮细胞凋亡.结论 脑出血后血肿周围神经细胞凋亡是脑出血后继发性神经损伤机制之一;黄芪注射液治疗脑出血,具有减轻脑水肿和神经细胞凋亡作用,以早期用药疗效更好.     

脑出血大鼠血肿周围脑组织含水量与基质金属蛋白酶-9、组织基质金属蛋白酶抑制剂-1及谷氨酸表达水平的关系

目的 探讨脑出血大鼠血肿周围脑组织含水量与基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制剂-1(TIMP-1)及谷氨酸表达水平的关系.方法 雄性Wistar大鼠48只,随机分为正常对照组(n=8)、假手术组(n=8)、脑出血组(n=32),脑出血组又分为脑出血后12h、24h、72 h、7d4个亚组,每亚组8只大鼠.采用自体血尾状核注入法制备脑出血模型.采用干湿重法测定脑含水量,免疫组化法检测血肿周围脑组织MMP-9、TIMP-1及谷氨酸的表达.结果 脑出血组各时间点亚组大鼠血肿周围脑组织含水量与MMP-9、TIMP-1及谷氨酸表达水平均显著高于正常对照组和假手术组(均P＜0.01).脑出血组中,72 h亚组大鼠脑组织含水量及MMP-9、TIMP-1表达水平最高(P ＜0.01);24 h亚组大鼠脑组织谷氨酸表达水平最高(P＜0.01).多重线性回归分析结果显示,脑组织含水量(Y)与脑组织MMP-9(X1)及谷氨酸(X3)表达水平呈直线关系,多元回归方程为Y=68.894+0.281X1-0.052X3.结论 脑出血后血肿周围组织含水量及MMP-9、TIMP-1、谷氨酸的表达水平明显增高,MMP-9、谷氨酸在脑出血后血肿周围组织水肿的发生发展中具有重要作用.     

二硫代氨基甲酸吡咯烷对实验性脑出血血肿周围脑组织含水量及水通道蛋白-9表达的影响

目的探讨二硫代氨基甲酸吡咯烷(PDTC)对实验性脑出血血肿周围脑组织含水量和水通道蛋白9(AQP9)表达的影响。方法将128只SD大鼠随机分成正常组、对照组、脑出血组及PDTC组,建立脑出血模型;制模2 h予PDTC组腹腔注射PDTC;通过干湿法和SABC法检测各组大鼠各时点脑组织含水量、AQP9表达。结果(1)脑出血组脑组织含水量出血侧在制模后4 h开始升高,72 h达高峰,持续到120 h后下降;出血对侧在4 h也升高,48 h达高峰;脑组织含水量较对照组明显增加,出血侧更明显(均P<0.01)。(2)脑出血组AQP9表达制模后4 h开始升高,72 h表达最强,120 h降低,较对照组明显增加,出血侧较出血对侧增加更明显(均P<0.01)。(3)PDTC组脑组织含水量和AQP9表达在制模后24 h开始各时间点较脑出血组明显降低(均P<0.01)。结论脑出血后脑组织含水量和AQP9表达均呈平行增加,PDTC干预对出血后脑组织含水量和AQP9表达有平行抑制作用,提示AQP9参与了脑出血后脑水肿的形成。     

实验性大鼠脑出血后TNF-α、ICAM-1的表达和脑水肿的研究

目的:探讨TNF-α、ICAM-1在大鼠脑出血后脑水肿中的表达及意义。方法:利用立体定向技术建立中等 量大鼠自体尾动脉血脑出血模型(50μl),于脑出血后6h、24h、48h、72h处死大鼠,进行脑含水量测定,并于脑出血后3h、 6h、12h、24h、48h、72h、7d处死大鼠,进行TNF-α、IGAM-1的免疫组化染色,并对结果进行统计处理。结果:大鼠脑出血 后脑水肿于48h达到高峰;大鼠脑组织表达TNF-α也于48h达到高峰,高于假手术组,分别为58．4±6．19和2±1．12,P <0．01;ICAM-1表达72h达高峰,与假手术组比较存在显著性差异,分别为7．8±0．84和0．8±0．84,P<0．01。结论: TNF-α、ICAM-1在大鼠脑出血后血肿周围表达的高峰与脑水肿高峰存在时间上的相关性,提示高表达的TNF-α、ICAM- 1可能参与了脑水肿形成。     

脑出血灶周HIF-1α的表达与脑水肿的实验研究

目的明确脑出血后灶周脑组织不同时间点HIF-1α蛋白的表达规律,在脑水肿的发生、发展过程中的可能作用,相关性及临床意义。方法本研究以不同时间点高血压脑出血患者开颅手术中取的脑出血灶周组织为病例组标本,按发病时间分为<6 h、6~24 h、24 h~3 d、>3 d组。以手术入颅路径上远离血肿处少许破坏的的脑组织做为对照组标本,通过干湿称重法测脑含水量,同时应用免疫组化染色方法,RT-PCR方法观察各组各时间点病灶周围脑组织HIF-1α的表达变化。结果 (1)脑组织水含量的变化,脑出血后脑水肿程度随出血时间的延长逐渐加重,在出血6 h内含水量即开始增高,24 h后较明显增高,3 d左右达到峰值,之后减轻(P<0.05)。(2)脑出血血肿灶周组织中HIF-1α圴有表达,对照组与出血组相比均有显著性意义(P<0.05),且出血组各时间点间比较均有差异(P<0.05)。出血6 h后免疫阳性细胞数开始增加,24 h~3 d组阳性细胞数最多,之后逐渐下降。HIF-1α与脑水肿成正相关。结论 (1)脑出血灶周HIF-1α的表达明显升高,与脑水肿密切相关。(2)HIF-1α的异常表达在高血压脑出血后脑水肿中起重要作用,促进脑水肿的发生,为脑出血的治疗提供新的靶点。     

补体在脑出血后脑组织损伤机制中的作用

目的研究补体C9在大鼠实验性脑出血(ICH)后血肿周围组织中的表达情况,探讨补体C9在ICH后脑水肿中的作用以及应用眼镜蛇毒因子(CVF)干预后对血肿周围组织C9表达及脑组织含水量变化的影响。方法采用立体定向技术,将自体不凝血注入大鼠尾状核制备ICH模型,将动物分为假手术组、出血组和CVF干预组,分别在不同时间断头取脑,连续切片分别作补体C9免疫组化染色和HE染色,并进行脑组织含水量测定(干湿重法)。结果ICH后2h血肿周围脑组织开始表达C9,24h达高峰。血肿周围脑组织含水量在ICH后2h开始增加(P<0.05),6h明显增加,24～72h达高峰(P<0.01),此后逐渐回落,1周基本恢复正常水平,脑组织含水量与C9的表达呈正相关关系(r=0.938,P<0.01);对侧半球相应部位及假手术对照组脑组织含水量没有明显变化;经CVF干预后,血肿周围组织C9表达明显下降,干预组与出血组之间比较有显著差异(P<0.01)。CVF干预组脑组织含水量明显低于常规ICH组(P<0.01)。结论脑出血后补体级联激活C9表达明显增加,并证明通过CVF干预后,C9表达下降,脑水肿减轻,能达到神经保护作用。     

COX-2在大鼠脑出血损伤机制中的实验研究

目的观察大鼠脑出血后环氧合酶2(COX-2)蛋白动态表达情况与血肿周围脑组织含水量的相互关系,及COX-2抑制剂对ICH大鼠脑水肿和神经功能的影响,探讨COX-2在ICH损伤机制中的作用。方法应用立体定向技术将自体血注入大鼠壳尾核制备脑出血模型,160雄性SD大鼠分为正常对照组、假手术组、脑出血组和尼美舒利治疗组。后3组每组50只,分6h、12h、24h、72h、7d五个时间点进行神经功能障碍评分,测定血肿周边脑组织含水量,免疫组织化学染色观察COX-2蛋白动态表达。结果脑出血组COX-2表达高于正常对照组(P<0.05),治疗组COX-2表达明显低于ICH组(P<0.05)。治疗组脑组织含水量明显低于ICH组(P<0.05)。治疗组各时间点神经功能评分明显高于ICH组(P<0.05)。ICH组COX-2蛋白表达与血肿周围脑组织含水量相关(r=0.911,P<0.001)。结论ICH后COX-2蛋白表达升高促进脑水肿形成,加重神经功能缺失。尼美舒利能抑制COX-2蛋白表达,减轻脑水肿,改善ICH后大鼠神经功能。     

Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat

Summary Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves.Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue, whose activity was revealed after-receptor blockade, had a similar threshold to the vasoconstrictor fibres.Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa.The preganglionic compound nerve action potential had four major components, S₁–S₄. S₁, S₂ and usually S₃ fibres were associated with membrane contraction; S₂, S₃ and sometimes S₁ fibres were associated with nasal vasoconstriction; and S₃, usually S₂ and occasionally S₁ fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S₄ fibres, may include fibres associated functionally with the three effectors.There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

Origins of the sympathetic innervation of the cervical end of the uterus in the rat

A retrograde neuronal tracer (Fast Blue) was injected in the cervical end of the uterine horn of virgin rats. The majority of the retrogradely labeled post-ganglionic sympathetic neurons were found in the sympathetic chain (74%). The superior mesenteric ganglia, inferior mesenteric ganglia and suprarenal ganglia accounted for 22, 3 and <1%, respectively. The distribution of neurons in the sympathetic chain labeled from the uterus resembles that described for other pelvic organs.     

Sexual pheromones and the evolution of the reward system of the brain: the chemosensory function of the amygdala

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemosensory role, but only view it as the core of the emotional brain. In this study, we propose that both roles of the amygdala are intimately linked since the amygdala is actually involved in mediating emotional responses to chemical signals. The amygdala is the only structure in the brain receiving pheromonal information directly from the accessory olfactory bulbs and we have shown in mice that males emit sexual pheromones that are innately attractive for females. In fact, sexual pheromones can be used as unconditioned stimuli to induce a conditioned attraction to previously neutral odorants as well as a conditioned place preference. Therefore, sexual pheromones should be regarded as natural reinforcers. Behavioural and pharmacological studies (reviewed here) have shown that the females' innate preference for sexual pheromones is not affected by lesions of the dopaminergic cells of the ventral tegmental area, and that the systemic administration of dopamine antagonists do not alter neither the attraction nor the reinforcing effects of these pheromones. Anatomical studies have shown that the vomeronasal amygdala gives rise to important projections to the olfactory tubercle and the islands of Calleja, suggesting that these amygdalo-striatal pathways might be involved in the reinforcing value of sexual pheromones.     

Topographical organization of the motoneuron pools that innervate the muscles of the pinna of the cat

The topographical organization of the 22 motoneuron pools that innervate the pinna muscles of the cat was examined by injecting the B-subunit of cholera toxin conjugated to horseradish peroxidase into individual muscles. All 22 pools are found in the facial nucleus, organized as rostro-caudally oriented columns, and arranged according to the action of the muscles they innervate. Pools innervating muscles that pull the pinna dorsally are located in the dorsal two thirds of the medio-dorsal subdivision, and those innervating muscles that pull the pinna ventrally are located in the ventral one half of the nucleus. Motoneurons innervating muscles that pull the pinna cranially are located laterally, those that pull the pinna caudally are located medio-ventrally, and those that change the shape of the pinna are located along the entire dorso-ventral extent in the center of the medio-dorsal subdivision. This topographical layout is consistent with the somatotopic organization of the entire facial nucleus as demonstrated in a variety of species. © 1995 Wiley-Liss, Inc.     

药物治疗与合并认知行为治疗对强迫症疗效的比较

目的探讨认知行为心理治疗(CBT)在强迫症(OCD)患者各亚型治疗中的有效性和规律性。方法本研究为临床对照研究。符合入组标准的强迫症患者按患者自愿原则分为两组,治疗观察3、6、12个月。疗效评定分别运用Yale-Brown强迫量表,自拟的自评好转程度量表和临床疗效评定。结果认知行为心理治疗合并药物治疗组31例,临床有效率70.9%,其中治愈率1.8%。单纯药物治疗组24例,临床有效率33.3%。Yale-Brown强迫量表和自评量表得分在6个月和12个月两组有显著差异(P<0.05)。其中强迫症亚型(怕脏型、反复检查型和反复担心型)的疗效比较,怕脏型在治疗3个月末两组间自评量表评分有显著性差异(P<0.05);反复担心型在治疗6个月末两组间Yale-Brown强迫量表总分有显著性差异(P<0.05);反复检查型两组间无统计学差异。结论认知行为心理治疗合并药物治疗强迫症的疗效明显优于单纯药物治疗。强迫症的亚型在治疗中的有效性次序为:反复担心型>怕脏型>反复检查型。     

Histochemical methods for the further characterisation of the tumourettes of the posterior lobe of the pituitary

Summary The granular cell tumourettes of the posterior lobe of the pituitary possess neuraminic acid containing carbohydrate. After removal of neuraminic acid with neuraminidase and exposure to FITC (Fluorescein isothiocyanate) labelled peanut agglutinin (Arachis hypogaea) (PNA), intracellular receptor structures could be demonstrated. The significance of the findings is discussed.